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Histoplasma Responses to Nutritional Immunity Imposed by Macrophage Activation

Identifieur interne : 000B63 ( Main/Exploration ); précédent : 000B62; suivant : 000B64

Histoplasma Responses to Nutritional Immunity Imposed by Macrophage Activation

Auteurs : Peter J. Brechting ; Chad A. Rappleye

Source :

RBID : PMC:6616858

Abstract

The fungal pathogen Histoplasma capsulatum resides within the phagosome of host phagocytic cells. Within this intracellular compartment, Histoplasma yeast replication requires the acquisition of several essential nutrients, including metal ions. Recent work has shown that while iron, zinc, and copper are sufficiently abundant in resting macrophages, cytokine activation of these host cells causes restriction of these metals from intracellular yeasts as a form of nutritional immunity. Faced with limited iron availability in the phagosome following macrophage activation by IFN-γ, Histoplasma yeasts secrete iron-scavenging siderophores and employ multiple strategies for reduction of ferric iron to the more physiologically useful ferrous form. IFN-γ activation of macrophages also limits availability of copper in the phagosome, forcing Histoplasma reliance on the high affinity Ctr3 copper importer for copper acquisition. GM-CSF activation stimulates macrophage production of zinc-chelating metallothioneins and zinc transporters to sequester zinc from Histoplasma yeasts. In response, Histoplasma yeasts express the Zrt2 zinc importer. These findings highlight the dynamics of phagosomal metal ion concentrations in host-pathogen interactions and explain one mechanism by which macrophages become a less permissive environment for Histoplasma replication with the onset of adaptive immunity.


Url:
DOI: 10.3390/jof5020045
PubMed: 31195617
PubMed Central: 6616858


Affiliations:


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Le document en format XML

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Responses to Nutritional Immunity Imposed by Macrophage Activation</title>
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Responses to Nutritional Immunity Imposed by Macrophage Activation</title>
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<p>The fungal pathogen
<italic>Histoplasma capsulatum</italic>
resides within the phagosome of host phagocytic cells. Within this intracellular compartment,
<italic>Histoplasma</italic>
yeast replication requires the acquisition of several essential nutrients, including metal ions. Recent work has shown that while iron, zinc, and copper are sufficiently abundant in resting macrophages, cytokine activation of these host cells causes restriction of these metals from intracellular yeasts as a form of nutritional immunity. Faced with limited iron availability in the phagosome following macrophage activation by IFN-γ,
<italic>Histoplasma</italic>
yeasts secrete iron-scavenging siderophores and employ multiple strategies for reduction of ferric iron to the more physiologically useful ferrous form. IFN-γ activation of macrophages also limits availability of copper in the phagosome, forcing
<italic>Histoplasma</italic>
reliance on the high affinity Ctr3 copper importer for copper acquisition. GM-CSF activation stimulates macrophage production of zinc-chelating metallothioneins and zinc transporters to sequester zinc from
<italic>Histoplasma</italic>
yeasts. In response,
<italic>Histoplasma</italic>
yeasts express the Zrt2 zinc importer. These findings highlight the dynamics of phagosomal metal ion concentrations in host-pathogen interactions and explain one mechanism by which macrophages become a less permissive environment for
<italic>Histoplasma</italic>
replication with the onset of adaptive immunity.</p>
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